Chemo-immunotherapy (Gemcitabine, Interferon-alpha 2b and p53 SLP) in Patients With Platinum-resistant Ovarian Cancer (CHIP)

Leiden University Medical Center (LUMC)

Status and phase: Completed; Phase 2; Phase 1

Conditions: Recurrent Ovarian Cancer

Treatments: Biological: p53 SLP; Drug: Interferon Alfa-2b

Study type: Interventional

Funder types: Other

Identifiers

NCT01639885

2010-023124-24 (EudraCT Number)

CHIP trial

Details and patient eligibility

About

This study investigates the feasibility and immunogenicity of the triple combination of gemcitabine, Peg-Intron and p53 SLP vaccination in patients with platinum-resistant ovarian cancer.

Full description

Recurrent ovarian cancer has a dismal prognosis and there is a pressing need to identify more efficient therapies. Ovarian cancer is highly immunogenic and good survival is tightly linked to the presence of tumor-infiltrating T cells and the absence of immunosuppressive immune cells. This anti-tumor immune response might be primed by chemotherapy.

Gemcitabine has immune-modulatory properties in addition to its direct cytotoxic effect in platinum resistant ovarian cancer. Additionally, Peg-Intron allows the full maturation of dendritic cells, thereby enhancing the anti-tumor response. Moreover, the tumor-associated self-antigen p53 is commonly over-expressed in ovarian cancer and can serve as a target for immunotherapy. Therefore, chemo-immunotherapy with gemcitabine and Peg-Intron plus/minus p53 SLP vaccination seems an attractive treatment for recurrent, p53+ ovarian cancer patients.

Enrollment: 15 patients

Sex: Female

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Histological proven epithelial ovarian cancer, peritoneal cavity or fallopian tube cancer (inclusive mucinous or clear cell tumors)
• Tumor over-expressing p53
• Progression of disease or relapse after previous therapy with platinum
• Measurable disease (RECIST 1.1) or elevated CA125 > 2 times the upper limit of normal within 3 months and confirmed
• Age ≥ 18 years
• WHO performance status 0-2
• Adequate bone marrow function: WBC ≥ 3.0 x 109/l, neutrophils ≥ 1.5 x 109/l, platelets ≥ 100 x 109/l
• Adequate liver function: bilirubin ≤ 1.5 x upper limit of normal (UNL) range, ALAT and/or ASAT ≤ 2.5 x UNL, Alkaline Phosphatase ≤5 x UNL
• Adequate renal function: the calculated creatinine clearance should be ≥ 50 mL/min
• Survival expectation > 3 months
• Patients must be accessible for treatment and follow-up
• Written informed consent according to the local Ethics Committee requirements

Exclusion criteria

• Previous malignancy within 5 years, with exception of a history of a previous basal cell carcinoma of the skin or pre-invasive carcinoma of the cervix.
• Serious other diseases as recent myocardial infarction, clinical signs of cardiac failure or clinically significant arrhythmias
• Known hypersensitivity reaction to any of the components of the treatment
• Pregnancy or lactating
• Medical or psychological condition which in the opinion of the investigator would not permit the patient to complete the study or sign meaningful informed consent

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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15 participants in 3 patient groups

Group 1

No Intervention group

Description:

Patients will receive standard care (gemcitabine)

Group 2

Experimental group

Description:

Patients will receive standard care (gemcitabine) combined with interferon-alpha 2b (Peg-Intron)

Treatment:

Drug: Interferon Alfa-2b

Drug: Interferon Alfa-2b

Group 3

Experimental group

Description:

Patients will receive standard care (gemcitabine) combined with interferon-alpha 2b (Peg-Intron) and p53 SLP vaccin

Treatment:

Biological: p53 SLP

Drug: Interferon Alfa-2b

Drug: Interferon Alfa-2b